Trial Outcomes & Findings for Dihydroartemisinin-Piperaquine in the Context of Antiretroviral Therapy (NCT NCT04487145)
NCT ID: NCT04487145
Last Updated: 2025-03-14
Results Overview
AUC 0-day42 (from time 0 to 42 days) for piperaquine
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
194 participants
Primary outcome timeframe
42 days
Results posted on
2025-03-14
Participant Flow
Single dose study only enrolled 20 children in L1 and 20 in C1 to evaluate the safety in the context of DP and LPV/r drug-drug interaction, only one dose of DP was given in the treatment group (L1). None of those children were included in the 5 groups in the 3-dose full study. So this is not a two-period design.
Participant milestones
| Measure |
HIV-uninfected Children (C3a)
30 HIV-uninfected children age 3-10 years not on ART will take standard 3 consecutive once-daily oral doses of DP (20/120mg tablets) based on weight per 2015 WHO guidelines for DP. The brand name Duocotexin will be used. PK samples are collected after the 3rd dose. Control group for E3 and L3.
Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure.
|
HIV-infected Children on LPV/R-based ART (L3)
30 HIV-infected children age 3 - 10 years on LPV/r-based ART for at least 10 days will take standard 3 consecutive once-daily oral doses of DP (20/120mg tablets) based on weight per 2015 WHO guidelines for DP. The brand name Duocotexin will be used.
Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure.
|
HIV-infected Children on EFV-based ART (E3)
30 HIV-infected children age 3 - 10 years on EFV-based ART for at least 10 days will take standard 3 consecutive once-daily oral doses of DP (20/120mg tablets) based on weight per 2015 WHO guidelines for DP. The brand name Duocotexin will be used.
Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure.
|
HIV-uninfected Children (C3b)
30 HIV-uninfected children age 11-17 years not on ART will take standard 3 consecutive once-daily oral doses of DP (20/120mg tablets) based on weight per 2015 WHO guidelines for DP. The brand name Duocotexin will be used. Control group for D3.
Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure.
|
HIV-infected Children on DTG-based ART (D3)
30 HIV-infected children age 11 - 17 years on DTG-based ART for at least 10 days will take standard 3 consecutive once-daily oral doses of DP (20/120mg tablets) based on weight per 2015 WHO guidelines for DP. The brand name Duocotexin will be used.
Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure.
|
HIV-uninfected Children (C1)
20 HIV-uninfected children age 3-10 years not on ART will take standard 3 consecutive once-daily oral doses of DP (20/120mg tablets) based on weight per 2015 WHO guidelines for DP. The brand name Duocotexin will be used. PK samples are collected after the 1st dose. Control group for L1.
|
HIV-infected Children on LPV/R-based ART (L1)
20 HIV-infected children age 3 - 10 years on LPV/r-based ART for at least 10 days will take one oral dose DP (20/120mg tablets) based on weight per 2015 WHO guidelines for DP. The brand name Duocotexin will be used
|
|---|---|---|---|---|---|---|---|
|
Single-dose Study for Safety Evaluation
STARTED
|
0
|
0
|
0
|
0
|
0
|
20
|
20
|
|
Single-dose Study for Safety Evaluation
COMPLETED
|
0
|
0
|
0
|
0
|
0
|
20
|
20
|
|
Single-dose Study for Safety Evaluation
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
3-dose Study
STARTED
|
30
|
30
|
31
|
32
|
31
|
0
|
0
|
|
3-dose Study
COMPLETED
|
30
|
30
|
30
|
30
|
30
|
0
|
0
|
|
3-dose Study
NOT COMPLETED
|
0
|
0
|
1
|
2
|
1
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Dihydroartemisinin-Piperaquine in the Context of Antiretroviral Therapy
Baseline characteristics by cohort
| Measure |
HIV-infected Children on EFV-based ART (E3)
n=30 Participants
30 HIV-infected children age 3 - 10 years on EFV-based ART for at least 10 days will take standard 3 consecutive once-daily oral doses of DP (20/120mg tablets) based on weight per 2015 WHO guidelines for DP. The brand name Duocotexin will be used.
Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure.
|
HIV-infected Children on DTG-based ART (D3)
n=30 Participants
30 HIV-infected children age 11 - 17 years on DTG-based ART for at least 10 days will take standard 3 consecutive once-daily oral doses of DP (20/120mg tablets) based on weight per 2015 WHO guidelines for DP. The brand name Duocotexin will be used.
Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure.
|
HIV-infected Children on LPV/R-based ART (L3)
n=30 Participants
30 HIV-infected children age 3 - 10 years on LPV/r-based ART for at least 10 days will take standard 3 consecutive once-daily oral doses of DP (20/120mg tablets) based on weight per 2015 WHO guidelines for DP. The brand name Duocotexin will be used.
Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure.
|
HIV-uninfected Children (C3a)
n=30 Participants
30 HIV-uninfected children age 3-10 years not on ART will take standard 3 consecutive once-daily oral doses of DP (20/120mg tablets) based on weight per 2015 WHO guidelines for DP. The brand name Duocotexin will be used. PK samples are collected after the 3rd dose. Control group for E3 and L3.
Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure.
|
HIV-uninfected Children (C3b)
n=30 Participants
30 HIV-uninfected children age 11-17 years not on ART will take standard 3 consecutive once-daily oral doses of DP (20/120mg tablets) based on weight per 2015 WHO guidelines for DP. The brand name Duocotexin will be used. Control group for D3.
Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure.
|
HIV-uninfected Children (C1)
n=20 Participants
20 HIV-uninfected children age 3-10 years not on ART will take standard 3 consecutive once-daily oral doses of DP (20/120mg tablets) based on weight per 2015 WHO guidelines for DP. The brand name Duocotexin will be used. PK samples are collected after the 1st dose. Control group for L1.
|
HIV-infected Children on LPV/R-based ART (L1)
n=20 Participants
20 HIV-infected children age 3 - 10 years on LPV/r-based ART for at least 10 days will take one oral dose DP (20/120mg tablets) based on weight per 2015 WHO guidelines for DP. The brand name Duocotexin will be used.
|
Total
n=190 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|---|
|
Age, Continuous
|
7.9 years
n=5 Participants
|
15.3 years
n=7 Participants
|
7.1 years
n=5 Participants
|
7.4 years
n=4 Participants
|
14.7 years
n=21 Participants
|
6.2 years
n=8 Participants
|
6.5 years
n=8 Participants
|
8.7 years
n=24 Participants
|
|
Sex: Female, Male
sex · Female
|
19 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
11 Participants
n=4 Participants
|
13 Participants
n=21 Participants
|
13 Participants
n=8 Participants
|
8 Participants
n=8 Participants
|
92 Participants
n=24 Participants
|
|
Sex: Female, Male
sex · Male
|
11 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
19 Participants
n=4 Participants
|
17 Participants
n=21 Participants
|
7 Participants
n=8 Participants
|
12 Participants
n=8 Participants
|
98 Participants
n=24 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=24 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=24 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=24 Participants
|
|
Race (NIH/OMB)
Black or African American
|
30 Participants
n=5 Participants
|
30 Participants
n=7 Participants
|
30 Participants
n=5 Participants
|
30 Participants
n=4 Participants
|
30 Participants
n=21 Participants
|
20 Participants
n=8 Participants
|
20 Participants
n=8 Participants
|
190 Participants
n=24 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=24 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=24 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=24 Participants
|
|
Region of Enrollment
Uganda
|
30 participants
n=5 Participants
|
30 participants
n=7 Participants
|
30 participants
n=5 Participants
|
30 participants
n=4 Participants
|
30 participants
n=21 Participants
|
20 participants
n=8 Participants
|
20 participants
n=8 Participants
|
190 participants
n=24 Participants
|
|
Weight
|
21.4 kg
n=5 Participants
|
48.7 kg
n=7 Participants
|
19.0 kg
n=5 Participants
|
23.6 kg
n=4 Participants
|
42.7 kg
n=21 Participants
|
20.1 kg
n=8 Participants
|
18.9 kg
n=8 Participants
|
25.0 kg
n=24 Participants
|
PRIMARY outcome
Timeframe: 42 daysPopulation: Only five arms in 3-dose study. because C1 and L1 were only for single-dose study to evaluate safety, and those participants were not in 3-dose study,
AUC 0-day42 (from time 0 to 42 days) for piperaquine
Outcome measures
| Measure |
HIV-infected Children on EFV-based ART (E3)
n=30 Participants
30 HIV-infected children age 3 - 10 years on EFV-based ART for at least 10 days will take standard 3 consecutive once-daily oral doses of DP (20/120mg tablets) based on weight per 2015 WHO guidelines for DP. The brand name Duocotexin will be used.
Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure.
|
HIV-infected Children on DTG-based ART (D3)
n=30 Participants
30 HIV-infected children age 11 - 17 years on DTG-based ART for at least 10 days will take standard 3 consecutive once-daily oral doses of DP (20/120mg tablets) based on weight per 2015 WHO guidelines for DP. The brand name Duocotexin will be used.
Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure.
|
HIV-infected Children on LPV/R-based ART (L3)
n=30 Participants
30 HIV-infected children age 3 - 10 years on LPV/r-based ART for at least 10 days will take standard 3 consecutive once-daily oral doses of DP (20/120mg tablets) based on weight per 2015 WHO guidelines for DP. The brand name Duocotexin will be used.
Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure.
|
HIV-uninfected Children (C3a)
n=30 Participants
30 HIV-uninfected children age 3-10 years not on ART will take standard 3 consecutive once-daily oral doses of DP (20/120mg tablets) based on weight per 2015 WHO guidelines for DP. The brand name Duocotexin will be used. PK samples are collected after the 3rd dose. Control group for E3 and L3.
Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure.
|
HIV-uninfected Children (C3b)
n=30 Participants
30 HIV-uninfected children age 11-17 years not on ART will take standard 3 consecutive once-daily oral doses of DP (20/120mg tablets) based on weight per 2015 WHO guidelines for DP. The brand name Duocotexin will be used. Control group for D3.
Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure.
|
|---|---|---|---|---|---|
|
AUC0-42day in 3-dose Study
|
4.47 hr.ug/mL
Interval 3.83 to 5.22
|
14.9 hr.ug/mL
Interval 12.0 to 18.2
|
49.7 hr.ug/mL
Interval 41.7 to 59.2
|
14.6 hr.ug/mL
Interval 12.7 to 16.7
|
19.2 hr.ug/mL
Interval 16.6 to 22.2
|
PRIMARY outcome
Timeframe: 42 daysPopulation: We only have five arms in 3-dose study. because C1 and L1 were only for single-dose study to evaluate safety. those participants were not in 3-dose study,
Safety of 3-dose DP regimens determined via-assessment of mean change in QT intervals from baseline; Here we reported mild adverse event defined as QTc F change\>30ms but \<60ms from baseline.
Outcome measures
| Measure |
HIV-infected Children on EFV-based ART (E3)
n=30 Participants
30 HIV-infected children age 3 - 10 years on EFV-based ART for at least 10 days will take standard 3 consecutive once-daily oral doses of DP (20/120mg tablets) based on weight per 2015 WHO guidelines for DP. The brand name Duocotexin will be used.
Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure.
|
HIV-infected Children on DTG-based ART (D3)
n=30 Participants
30 HIV-infected children age 11 - 17 years on DTG-based ART for at least 10 days will take standard 3 consecutive once-daily oral doses of DP (20/120mg tablets) based on weight per 2015 WHO guidelines for DP. The brand name Duocotexin will be used.
Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure.
|
HIV-infected Children on LPV/R-based ART (L3)
n=30 Participants
30 HIV-infected children age 3 - 10 years on LPV/r-based ART for at least 10 days will take standard 3 consecutive once-daily oral doses of DP (20/120mg tablets) based on weight per 2015 WHO guidelines for DP. The brand name Duocotexin will be used.
Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure.
|
HIV-uninfected Children (C3a)
n=30 Participants
30 HIV-uninfected children age 3-10 years not on ART will take standard 3 consecutive once-daily oral doses of DP (20/120mg tablets) based on weight per 2015 WHO guidelines for DP. The brand name Duocotexin will be used. PK samples are collected after the 3rd dose. Control group for E3 and L3.
Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure.
|
HIV-uninfected Children (C3b)
n=30 Participants
30 HIV-uninfected children age 11-17 years not on ART will take standard 3 consecutive once-daily oral doses of DP (20/120mg tablets) based on weight per 2015 WHO guidelines for DP. The brand name Duocotexin will be used. Control group for D3.
Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure.
|
|---|---|---|---|---|---|
|
QTcF in 3-dose Study
|
0 Participants
|
3 Participants
|
8 Participants
|
2 Participants
|
2 Participants
|
PRIMARY outcome
Timeframe: day 2-28Population: We only have five arms in phase 2. because C1 and L1 were only for phase 1 safety evaluation. those participants were not in phase 2 study,
Area under concentration -time curve from pre-3rd dose to day 28
Outcome measures
| Measure |
HIV-infected Children on EFV-based ART (E3)
n=30 Participants
30 HIV-infected children age 3 - 10 years on EFV-based ART for at least 10 days will take standard 3 consecutive once-daily oral doses of DP (20/120mg tablets) based on weight per 2015 WHO guidelines for DP. The brand name Duocotexin will be used.
Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure.
|
HIV-infected Children on DTG-based ART (D3)
n=30 Participants
30 HIV-infected children age 11 - 17 years on DTG-based ART for at least 10 days will take standard 3 consecutive once-daily oral doses of DP (20/120mg tablets) based on weight per 2015 WHO guidelines for DP. The brand name Duocotexin will be used.
Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure.
|
HIV-infected Children on LPV/R-based ART (L3)
n=30 Participants
30 HIV-infected children age 3 - 10 years on LPV/r-based ART for at least 10 days will take standard 3 consecutive once-daily oral doses of DP (20/120mg tablets) based on weight per 2015 WHO guidelines for DP. The brand name Duocotexin will be used.
Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure.
|
HIV-uninfected Children (C3a)
n=30 Participants
30 HIV-uninfected children age 3-10 years not on ART will take standard 3 consecutive once-daily oral doses of DP (20/120mg tablets) based on weight per 2015 WHO guidelines for DP. The brand name Duocotexin will be used. PK samples are collected after the 3rd dose. Control group for E3 and L3.
Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure.
|
HIV-uninfected Children (C3b)
n=30 Participants
30 HIV-uninfected children age 11-17 years not on ART will take standard 3 consecutive once-daily oral doses of DP (20/120mg tablets) based on weight per 2015 WHO guidelines for DP. The brand name Duocotexin will be used. Control group for D3.
Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure.
|
|---|---|---|---|---|---|
|
AUC0-day28 in 3-dose Study
|
4.33 hr.ug/mL
Interval 3.71 to 5.06
|
12.7 hr.ug/mL
Interval 10.3 to 15.7
|
41.6 hr.ug/mL
Interval 34.8 to 49.9
|
12.5 hr.ug/mL
Interval 10.9 to 14.4
|
16.4 hr.ug/mL
Interval 14.1 to 19.1
|
PRIMARY outcome
Timeframe: day 2-28Population: We only have five arms in 3-dose study. because C1 and L1 were only for single-dose study to evaluate safety. Those participants were not in 3-dose study,
maximal piperaquine concentration post the 3rd dose (day 2-42)
Outcome measures
| Measure |
HIV-infected Children on EFV-based ART (E3)
n=30 Participants
30 HIV-infected children age 3 - 10 years on EFV-based ART for at least 10 days will take standard 3 consecutive once-daily oral doses of DP (20/120mg tablets) based on weight per 2015 WHO guidelines for DP. The brand name Duocotexin will be used.
Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure.
|
HIV-infected Children on DTG-based ART (D3)
n=30 Participants
30 HIV-infected children age 11 - 17 years on DTG-based ART for at least 10 days will take standard 3 consecutive once-daily oral doses of DP (20/120mg tablets) based on weight per 2015 WHO guidelines for DP. The brand name Duocotexin will be used.
Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure.
|
HIV-infected Children on LPV/R-based ART (L3)
n=30 Participants
30 HIV-infected children age 3 - 10 years on LPV/r-based ART for at least 10 days will take standard 3 consecutive once-daily oral doses of DP (20/120mg tablets) based on weight per 2015 WHO guidelines for DP. The brand name Duocotexin will be used.
Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure.
|
HIV-uninfected Children (C3a)
n=30 Participants
30 HIV-uninfected children age 3-10 years not on ART will take standard 3 consecutive once-daily oral doses of DP (20/120mg tablets) based on weight per 2015 WHO guidelines for DP. The brand name Duocotexin will be used. PK samples are collected after the 3rd dose. Control group for E3 and L3.
Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure.
|
HIV-uninfected Children (C3b)
n=30 Participants
30 HIV-uninfected children age 11-17 years not on ART will take standard 3 consecutive once-daily oral doses of DP (20/120mg tablets) based on weight per 2015 WHO guidelines for DP. The brand name Duocotexin will be used. Control group for D3.
Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure.
|
|---|---|---|---|---|---|
|
Cmax for Piperaquine in 3-dose Study
|
243 ng/mL
Interval 202.0 to 292.0
|
285 ng/mL
Interval 224.0 to 363.0
|
491 ng/mL
Interval 397.0 to 608.0
|
218 ng/mL
Interval 175.0 to 272.0
|
272 ng/mL
Interval 221.0 to 334.0
|
OTHER_PRE_SPECIFIED outcome
Timeframe: <24hrPopulation: C1 and L1 were only for phase 1 safety evaluation, and those participants (n= 20 each arm) were not in phase 2 study,
Cmax for piperaquine: Maximal concentration in single-dose study to evaluate Safety
Outcome measures
| Measure |
HIV-infected Children on EFV-based ART (E3)
n=20 Participants
30 HIV-infected children age 3 - 10 years on EFV-based ART for at least 10 days will take standard 3 consecutive once-daily oral doses of DP (20/120mg tablets) based on weight per 2015 WHO guidelines for DP. The brand name Duocotexin will be used.
Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure.
|
HIV-infected Children on DTG-based ART (D3)
n=20 Participants
30 HIV-infected children age 11 - 17 years on DTG-based ART for at least 10 days will take standard 3 consecutive once-daily oral doses of DP (20/120mg tablets) based on weight per 2015 WHO guidelines for DP. The brand name Duocotexin will be used.
Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure.
|
HIV-infected Children on LPV/R-based ART (L3)
30 HIV-infected children age 3 - 10 years on LPV/r-based ART for at least 10 days will take standard 3 consecutive once-daily oral doses of DP (20/120mg tablets) based on weight per 2015 WHO guidelines for DP. The brand name Duocotexin will be used.
Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure.
|
HIV-uninfected Children (C3a)
30 HIV-uninfected children age 3-10 years not on ART will take standard 3 consecutive once-daily oral doses of DP (20/120mg tablets) based on weight per 2015 WHO guidelines for DP. The brand name Duocotexin will be used. PK samples are collected after the 3rd dose. Control group for E3 and L3.
Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure.
|
HIV-uninfected Children (C3b)
30 HIV-uninfected children age 11-17 years not on ART will take standard 3 consecutive once-daily oral doses of DP (20/120mg tablets) based on weight per 2015 WHO guidelines for DP. The brand name Duocotexin will be used. Control group for D3.
Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure.
|
|---|---|---|---|---|---|
|
Cmax for Piperaquine in Single-dose Study
|
96.3 ng/mL
Interval 61.6 to 151.0
|
208 ng/mL
Interval 145.0 to 299.0
|
—
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 1 dayPopulation: Phase 1 study for safety evaluation was done with two arms (C1 and L1), and those participants (n= 20 each arm) were not in phase 2 study,
AUC 0-24h (from time 0 to 24h) for piperaquine in single-dose study to evaluate safety.
Outcome measures
| Measure |
HIV-infected Children on EFV-based ART (E3)
n=20 Participants
30 HIV-infected children age 3 - 10 years on EFV-based ART for at least 10 days will take standard 3 consecutive once-daily oral doses of DP (20/120mg tablets) based on weight per 2015 WHO guidelines for DP. The brand name Duocotexin will be used.
Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure.
|
HIV-infected Children on DTG-based ART (D3)
n=20 Participants
30 HIV-infected children age 11 - 17 years on DTG-based ART for at least 10 days will take standard 3 consecutive once-daily oral doses of DP (20/120mg tablets) based on weight per 2015 WHO guidelines for DP. The brand name Duocotexin will be used.
Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure.
|
HIV-infected Children on LPV/R-based ART (L3)
30 HIV-infected children age 3 - 10 years on LPV/r-based ART for at least 10 days will take standard 3 consecutive once-daily oral doses of DP (20/120mg tablets) based on weight per 2015 WHO guidelines for DP. The brand name Duocotexin will be used.
Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure.
|
HIV-uninfected Children (C3a)
30 HIV-uninfected children age 3-10 years not on ART will take standard 3 consecutive once-daily oral doses of DP (20/120mg tablets) based on weight per 2015 WHO guidelines for DP. The brand name Duocotexin will be used. PK samples are collected after the 3rd dose. Control group for E3 and L3.
Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure.
|
HIV-uninfected Children (C3b)
30 HIV-uninfected children age 11-17 years not on ART will take standard 3 consecutive once-daily oral doses of DP (20/120mg tablets) based on weight per 2015 WHO guidelines for DP. The brand name Duocotexin will be used. Control group for D3.
Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure.
|
|---|---|---|---|---|---|
|
AUC0-24h for Piperaquine in Single-dose Study
|
1.00 hr.ug/mL
Interval 0.73 to 1.37
|
1.89 hr.ug/mL
Interval 1.33 to 2.69
|
—
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 28 daysPopulation: Single-dose study for safety evaluation was done with two arms (C1 and L1), and those participants (n= 20 each arm) were not in 3-dose full study,
Cardiotoxicity associated with PQ is QT interval prolongation. Electrocardiogram (ECG) will be performed to provide data on QT intervals in msec. Reported if QTcF\>30ms
Outcome measures
| Measure |
HIV-infected Children on EFV-based ART (E3)
n=20 Participants
30 HIV-infected children age 3 - 10 years on EFV-based ART for at least 10 days will take standard 3 consecutive once-daily oral doses of DP (20/120mg tablets) based on weight per 2015 WHO guidelines for DP. The brand name Duocotexin will be used.
Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure.
|
HIV-infected Children on DTG-based ART (D3)
n=20 Participants
30 HIV-infected children age 11 - 17 years on DTG-based ART for at least 10 days will take standard 3 consecutive once-daily oral doses of DP (20/120mg tablets) based on weight per 2015 WHO guidelines for DP. The brand name Duocotexin will be used.
Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure.
|
HIV-infected Children on LPV/R-based ART (L3)
30 HIV-infected children age 3 - 10 years on LPV/r-based ART for at least 10 days will take standard 3 consecutive once-daily oral doses of DP (20/120mg tablets) based on weight per 2015 WHO guidelines for DP. The brand name Duocotexin will be used.
Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure.
|
HIV-uninfected Children (C3a)
30 HIV-uninfected children age 3-10 years not on ART will take standard 3 consecutive once-daily oral doses of DP (20/120mg tablets) based on weight per 2015 WHO guidelines for DP. The brand name Duocotexin will be used. PK samples are collected after the 3rd dose. Control group for E3 and L3.
Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure.
|
HIV-uninfected Children (C3b)
30 HIV-uninfected children age 11-17 years not on ART will take standard 3 consecutive once-daily oral doses of DP (20/120mg tablets) based on weight per 2015 WHO guidelines for DP. The brand name Duocotexin will be used. Control group for D3.
Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure.
|
|---|---|---|---|---|---|
|
QTcF in Single-dose Safety Study
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 42 daysZ-score is the anthropomorphic indicator of malnutrition measured as weight-for age (WFA). Children will be characterized as a) "stunted" but not underweight \[i.e. weight for age (WFA) z-score\>-2); b) underweight, but not stunted (WFA z-score ≤-2); or c) of normal nutritional status (WFA z-scores \>-1).
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: 3 daysDHA AUC0-8hr post the 1st dose is compared to AUC0-8hr post the 3rd dose
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: 4 daysTo assess prevalence of CYP2B6 pharmacogenetic variants and their impact on EFV PK
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: 42 daysChildren will be characterized as a) "stunted" but not underweight \[i.e. height for age (HFA) z-score ≤-2); b) underweight, but not stunted (HFA z-score\>-2); or c) of normal nutritional status (HFA z-scores \>-1).
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: 4 daysCompare the trough EFV concentration on day 0 (pre-DP and EFV doses) to day 3 (24hr after DP and EFV doses)
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: 4 daysPre-ART sample to quantify trough of DTG, sampled collected via venipuncture on Day 0, 2, \& 3 to allow for comparisons of DTG level.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: 4 daysPre-ART sample to quantify trough of LPV/r, sampled collected via venipuncture on Day 0, 2, \& 3 to allow for comparisons of LPV/r level.
Outcome measures
Outcome data not reported
Adverse Events
HIV-infected Children on EFV-based ART (E3)
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
HIV-infected Children on DTG-based ART (D3)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
HIV-infected Children on LPV/R-based ART (L3)
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
HIV-uninfected Children (C3a)
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
HIV-uninfected Children (C3b)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
HIV-uninfected Children (C1)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
HIV-infected Children on LPV/R-based ART (L1)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
HIV-infected Children on EFV-based ART (E3)
n=30 participants at risk
30 HIV-infected children age 3 - 10 years on EFV-based ART for at least 10 days will take standard 3 consecutive once-daily oral doses of DP (20/120mg tablets) based on weight per 2015 WHO guidelines for DP. The brand name Duocotexin will be used.
Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure.
|
HIV-infected Children on DTG-based ART (D3)
n=30 participants at risk
30 HIV-infected children age 11 - 17 years on DTG-based ART for at least 10 days will take standard 3 consecutive once-daily oral doses of DP (20/120mg tablets) based on weight per 2015 WHO guidelines for DP. The brand name Duocotexin will be used.
Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure.
|
HIV-infected Children on LPV/R-based ART (L3)
n=30 participants at risk
30 HIV-infected children age 3 - 10 years on LPV/r-based ART for at least 10 days will take standard 3 consecutive once-daily oral doses of DP (20/120mg tablets) based on weight per 2015 WHO guidelines for DP. The brand name Duocotexin will be used.
Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure.
|
HIV-uninfected Children (C3a)
n=30 participants at risk
30 HIV-uninfected children age 3-10 years not on ART will take standard 3 consecutive once-daily oral doses of DP (20/120mg tablets) based on weight per 2015 WHO guidelines for DP. The brand name Duocotexin will be used. PK samples are collected after the 3rd dose. Control group for E3 and L3.
Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure.
|
HIV-uninfected Children (C3b)
n=30 participants at risk
30 HIV-uninfected children age 11-17 years not on ART will take standard 3 consecutive once-daily oral doses of DP (20/120mg tablets) based on weight per 2015 WHO guidelines for DP. The brand name Duocotexin will be used. Control group for D3.
Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure.
|
HIV-uninfected Children (C1)
n=20 participants at risk
20 HIV-uninfected children age 3-10 years not on ART will take standard 3 consecutive once-daily oral doses of DP (20/120mg tablets) based on weight per 2015 WHO guidelines for DP. The brand name Duocotexin will be used. PK samples are collected after the 1st dose. Control group for L1
|
HIV-infected Children on LPV/R-based ART (L1)
n=20 participants at risk
20 HIV-infected children age 3 - 10 years on LPV/r-based ART for at least 10 days will take one oral dose DP (20/120mg tablets) based on weight per 2015 WHO guidelines for DP. The brand name Duocotexin will be used
.
|
|---|---|---|---|---|---|---|---|
|
Cardiac disorders
QTcF prolongation
|
0.00%
0/30 • 42 days
|
0.00%
0/30 • 42 days
|
26.7%
8/30 • Number of events 8 • 42 days
|
6.7%
2/30 • Number of events 2 • 42 days
|
0.00%
0/30 • 42 days
|
0.00%
0/20 • 42 days
|
0.00%
0/20 • 42 days
|
|
Blood and lymphatic system disorders
iron deficient anemia
|
3.3%
1/30 • Number of events 1 • 42 days
|
0.00%
0/30 • 42 days
|
0.00%
0/30 • 42 days
|
0.00%
0/30 • 42 days
|
0.00%
0/30 • 42 days
|
0.00%
0/20 • 42 days
|
0.00%
0/20 • 42 days
|
Additional Information
Liusheng Huang(Co-Investigator and Drug Research Unit Co-Director)
University of Califronia San Francisco
Phone: 415-502-2594
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place